The presence of a 1.4 x 10 to the 6th power dalton double-stranded RNA in intracellular virus-like particles (the K1 killer plasmid or killer virus) in Saccharomyces cerevisiae enables cells to secrete a protein toxin and be immune to this toxin. We have defined 28 chromosomal genes (called makl, ...) needed to replicate or maintain the killer plasmid. We have found effects of regulatory chromosomal mutations affecting the killer plasmid (ski mutations) on the interference phenomenon by defective-interfering plasmid mutants. A second killer plasmid, called K2, is excluded by the K1 plasmid. We have found a new plasmid, called (EXL), which is not a killer plasmid but also excludes K2. Yet another plasmid, called (NEX), prevents this effect of (EXL) on K2. A chromosomal gene, man1, is needed to maintain (NEX). Another chromosomal gene, mkt1, is required K2 maintenance if (NEX) is present.